Introduction: Obesity increases the risk of salt sensitive hypertension and kidney damage. AcSDKP is a natural tetrapeptide with anti-inflammatory and antifibrotic properties but its effect on obesity-related salt sensitive hypertension and renal damage is unknown. Hypothesis: AcSDKP prevents high-sodium diet (HSD) induced hypertension and kidney damage in obese rats. Methods: Eight-week-old Zucker obese rats (ZOR) and Zucker lean rats (ZLR) were treated with AcSDKP (1.6 mg/kg/day infused via osmotic minipumps) while maintained on either normal-sodium diet (NSD; 0.4%) or high-sodium diet (HSD; 4%) for 8 wk. Rats were divided into following six groups: ZOR+vehicle, ZOR+HSD, ZOR+HSD+AcSDKP, ZLR+vehicle, ZLR+ HSD, and ZLR+HSD+AcSDKP. Systolic blood pressure (SBP) was measured by tail cuff method. 24-hour urine collection was done to measure albuminuria as a marker of renal damage. Renal fibrosis (collagen content in the kidney) was measured by hydroxyproline assay. Medullary and cortical interstitial fibrosis was measured by picrosirius red staining. Results: are summarized in Table 1. HSD increased SBP in ZOR but not in ZLR. AcSDKP treatment prevented HSD induced increase in BP in ZOR. HSD increased renal collagen content both in ZOR and ZLR and AcSDKP treatment decreased it. Increased interstitial fibrosis induced by high salt diet was confirmed by PSR staining in both cortical and medullary region and AcSDKP prevented this increase. Albuminuria in ZOR was significantly higher than ZLR, however neither high salt nor AcSDKP treatment was unable to normalize it. Conclusion: Chronic treatment with AcSDKP prevents high salt-induced hypertension and renal fibrosis in ZOR.