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As a result of the island's long isolation from neighboring continents, Madagascar is home to a vast array of plants and animals; many found nowhere else on Earth. Approximately 80% of all plant and animal species found in Madagascar are endemic; including the lemur-infra order of primates, the carnivorous fossa and three avian families. This distinctive ecology has led some ecologists to refer to Madagascar as the "eighth continent", and the island has been classified, by Conservation International, as a biodiversity hotspot. Over 10,000 plant species are native to Madagascar, of which 90% are found nowhere else in the world. Seven plant families are only found here, the highest number of any biodiversity hotspot in the world. The plant family didiereaceae composed of four genera and 11 species is limited to the spiny forests of southwestern Madagascar. Four-fifths of the world's pachypodium species are endemic to the island. Three-fourths of Madagascar's 960 orchid species are found here alone, as are six of the world's eight baobab species. The island is also home to around 170 palm species, three times as many as are found on mainland Africa; 165 of these are endemic. Many native plant species are used as effective herbal remedies for a variety of afflictions, including the Madagascar periwinkle, which has recently been established as the most effective treatment for leukemia and Hodgkin’s disease. The traveler’s palm, endemic to the eastern rain forests, is highly iconic of Madagascar and is featured in the national emblem as well as the Madagascar Airline logo.

The ring-tailed lemur is one of around 100 known species and subspecies of lemur found only in Madagascar. The Aye Aye is the world’s largest (and weirdest!) nocturnal primate and uses echolocation to locate food. Lemurs have been characterized as "Madagascar's flagship mammal species", by Conservation International. In the absence of monkeys and other competitors, these primates have adapted to a wide range of habitats and diversified into numerous species. As of 2008, there are officially 99 species and subspecies of lemur, 39 of which have been described by zoologists between the years 2000 and 2008. They are almost all classified as rare, vulnerable, or endangered. At least 17 species of lemur have become extinct since man arrived on Madagascar, all of which were larger than the surviving lemur species.

The biodiversity of fauna in Madagascar extends beyond pro-simians to the wider animal population. A number of other mammals, including the cat-like fossa, are endemic to Madagascar. Over 300 species of bird have been recorded on the island, of which over 60% (including four families and 42 genera) are endemic. The few families and genera of reptile that have reached Madagascar have diversified into more than 260 species, with over 90% of these being endemic (including one endemic family). The island is home to two-thirds of the world's chameleon species, and researchers have proposed that Madagascar may represent the origin of all chameleon species.

Endemic fishes on Madagascar include two families, 14 genera and over 100 species primarily inhabiting the island's freshwater lakes and rivers. Although invertebrate species remain poorly studied on Madagascar relative to other wildlife, researchers have found high rates of endemism among known species. All 651 species of terrestrial snail are endemic, as are a majority of the island's butterflies, scarab beetles, lacewings, spiders and dragonflies