To elucidate the involvement of cyclooxygenase (COX) in degradation of aggregated protein in diabetic glomeruli, we used streptozotocin (STZ)-induced diabetic mice and aggregated bovine serum albumin (a-BSA) as a model protein. There was a higher deposition of a-BSA in diabetic glomeruli compared to normal glomeruli 18 h after a-BSA injection at 4 and 8 weeks after STZ. Degradation of a-BSA was confirmed using isolated glomeruli. Diabetic glomeruli produced prostaglandin E(2) (PGE(2)) more than normal glomeruli in the basal level at 8 weeks. a-BSA caused further increase of PGE(2) production in normal glomeruli, but not in diabetic glomeruli. Niflimic acid, a selective COX-2 inhibitor, reduced PGE(2) production of normal glomeruli in the a-BSA loading group, but not that in the control group. In diabetic glomeruli, niflimic acid reduced PGE(2) production in both the control group and a-BSA loading group. In normal glomeruli, a-BSA increased expressions of both COX-2 mRNA and protein. However, in diabetic glomeruli, a-BSA increased COX-2 mRNA expression but not COX-2 protein expression. These results suggest that retarded degradation of aggregated protein in diabetic glomeruli is associated with lack of further expression of COX-2 protein and further production of PGE(2) in response to aggregated protein.