The relationship between trypsin-inhibitory activity (TIA) and the nephrotoxic effects of mercuric chloride (HgCl2)—as illustrated by proteinuria and by a drop in the glomerular filtration rate (GFR) measured by creatinine clearance test (CCT)—was investigated in Wistar rats. HgCl2, 150 or 250μg/100 g BW per day was injected intraperitoneally three times a week for 2 weeks. Both groups showed a significant degree of proteinuria and urinary TIA. Group B (250μg HgCl2/100 g BW) displayed a greater drop in GFR than group A (150μg HgCl2/100 g BW). The urinary TIA was significantly correlated with proteinuria (group A:r = 0.87, group B:r = 0.84), but it was also significantly inversely correlated with the CCT (A:r = -0.96; B:r = -0.88). In conclusion: these results suggest that increased urinary TIA may be involved in and indicative of the pathogenesis of mercuric chloride induced nephrotoxicity.