The blaze broke out overnight on the sixth floor of the building that houses the museum in central Delhi and rapidly engulfed the other floors, a fire official said.
Thirty-five fire fighters battled for hours to extinguish the blaze and five of them were taken to hospital suffering smoke inhalation, a fire department official told AFP.
Environment minister Prakash Javadekar said officials had yet to determine the full extent of the damage but old collections had been destroyed.
“This is a real loss. This loss cannot be counted in rupees. Some very old species of flora and fauna were there,” Javadekar told reporters outside the museum, adding some were rare.
He also ordered an immediate safety audit of the country’s 34 major museums.
The museum, inaugurated in 1978, contained preserved specimens of butterflies, frogs, snakes, lizards as well as mounted specimens of tigers and leopards.
Fire accidents are common in hot summer months across India, with short circuits in dilapidated buildings often triggering blazes.