The present study was undertaken with the objectives to evaluate the specificity of different diagnostic tests in clinical cases of rabies, to evaluate pathomorphological changes in experimentally induced rabies with fixed and Street virus in mice and to determine the expression of proinflammatory cytokines and their relation to clearance of virus from brain tissue in mice. A total of 114 brain samples of rabies were collected from suspected cases and these samples were subjected to Seller’s staining, FAT, dRIT and RT-PCR for the diagnosis of rabies. Of these 81 samples were tested positive by different tests with an overall rabies incidence of 71.05 per cent. The results of direct microscopic examination for Negri bodies by Seller’s staining technique detected Negri bodies in 64 brain samples out of 114 brain samples from different species with 56.14 per cent positivity, where as FAT and dRIT detected 77 (67.54%) rabies positive cases. The positive and negative samples by Seller’s staining, FATand dRIT further confirmed with the conventional RT-PCR which detected rabies in 81 cases.