PRR expression is upregulated in Diabetic nephropathy (DN) and contributes to development of podocyte inflammation. We hypothesized that PRR contributes to podocyte inflammation via activation of IL-1β-COX-2-NF-κB signaling pathway. Mouse podocytes were cultured in normal (NG, 5 mM) or high (HG, 25mM) D-glucose individually or treated with either scrambled siRNA (Scr) or PRR siRNA for 3 days. Proteins expressions are shown below. Scr siRNA did not influence mRNA or protein expressions of PRR, COX-2, or NF-κB. Compared to NG, HG significantly increased mRNA and protein expressions of PRR (172%, p<0.01; 37%, p<0.05), IL-1β (87%, p<0.05; 20%, p<0.05), COX-2 (200 %, p<0.05; 71%, p<0.05), and NF-κB (248%, p<0.001; 101%, p<0.05), respectively. Compared to HG, cells treated with HG and PRR siRNA demonstrated reduction in mRNA and protein expressions of PRR (62%, p<0.01; 58%, p<0.05), IL-1β (46%, p<0.05; 8%, p<0.05), COX-2 (37%, p<0.05; 47%, p<0.05), and NF-κB (34%, p<0.05; 54%, p<0.05). We conclude that PRR-IL-1β-COX-2-NF-κB pathway activation is involved in HG induces podocyte inflammation.