Gentamicin which is an aminoglycoside antibiotic has known to compete with Cellular calcium influx in several biological processes and it has been proven beyond doubt that it is an N- type calcium channel blocker. The present study was planned with the aim to compare the analgesic effect of Gentamicin with the renowned analgesic drug aspirin in thermally induced Pain models of rats and mice. In our study, with regard to tail flick method, gentamicin at 160 µg dose showed a higher antinociceptive activity compared to aspirin at 60 min and 120 min in rats and at 90 min and 120 min in mice which indicates that it has a persistent analgesic action that might be explained due to its long duration of action. From the above data generated it can be concluded that gentamicin is showing the comparable analgesic effect as that of aspirin in the tail flick method when administered to rats and mice. The study also concluded that the analgesic effect of the antibiotics can be used to supplement the other analgesic drugs thus minimising the adverse effect in some populations.