Enhanced expression of cyclooxygenase 2 (COX2) in podocytes contributes to glomerular injury in diabetic kidney disease, but some basal level of podocyte COX2 expression might be required to promote podocyte attachment and/or survival. To investigate the role of podocyte COX2 expression in diabetic kidney disease, we deleted COX2 specifically in podocytes in a mouse model of type 1 diabetes mellitus (Akita mice). Podocyte specific knockout (KO) of COX2 did not affect renal morphology or albuminuria in non-diabetic mice. Albuminuria was significantly increased in wild type (WT) and KO Akita mice compared to non-diabetic controls, and the increase in albuminuria was significantly greater in KO Akita mice compared to WT Akita mice at both 16- and 20-weeks of age. At the 20-week time point, mesangial expansion was also increased in WT and KO Akita mice compared to non-diabetic animals, and these histologic abnormalities were not improved by KO of COX2. Tubular injury was seen only in diabetic mice, but there were no significant differences between groups. Thus, KO of COX2 enhanced albuminuria and did not improve the histopathologic features of diabetic kidney disease. These data suggest that: 1. KO of COX2 in podocytes does not ameliorate diabetic kidney disease in Akita mice, and 2. Some basal level of podocyte COX2 expression in podocytes is necessary to attenuate the adverse effects of diabetes on glomerular filtration barrier function.