Peripheral CB1R blockade abolishes diabetes-induced renal injury, inflammation, and tubule-interstitial fibrosis. The diabetes-induced elevations in urinary excretion levels of (A) clusterin, cystatin C, and IP-10 and (B) kidney TNFα mRNA and (C) renal protein expression of these injury and inflammatory markers were normalized in mice treated chronically with JD5037 or SLV319. (D) Representative renal IHC staining of clusterin, cystatin C, TNFα, and IP-10 from each group. Original magnification, ×40. Scale bar, 50 μm. Fibrosis was determined by measuring the (E) renal mRNA and (F and G) protein expression levels of collagen-1, collagen-3, TIMP-1, and fibronectin-1. Note that diabetes-induced renal fibrosis was completely ameliorated by chronic JD5037 and SLV319 treatment. Representative renal IHC staining from each group. Data represent the mean±SEM from eight to ten mice per group. Original magnification, ×40. Scale bar, 50 μm. *P<0.05 relative to the corresponding control group treated with Veh; #P<0.05 relative to the corresponding STZ group treated with Veh.