AIM: Nimesulide, a preferential COX-2 inhibitor has 20 times more selectivity towards COX-2 than that of COX-1. COX-2 selective inhibitors cause frequent nephrotoxicity and hepatotoxicity following their usage. This proposes a physiological role of COX-2 in kidney and liver. Not much attention has been focused on the role of COX-2 with respect to reproduction especially in male reproduction, and the available information is scanty. AIMs and Objectives: The present study aims to investigate the adverse effects of nimesulide in the vas deferens thereby indirectly assess the role of COX-2 in male reproductive tract. MATERIAL AND METHODS: Nimesulide was administered orally and the animals were maintained for different time periods prior to sacrifice. RESULTS: The vas deferens of nimesulide treated mice showed extensive histopathological changes such as vacoulation and exfoliation of cells in the epithelial layer. CONCLUSION: Nimesulide administration leads to cytotoxic effects suggestive of apoptosis in the vas deferens of mice.