Objective To examine the role and mechanism of clopidogrel in the development????????? of salt-sensitive hypertension. Methods Two-month-old Dahl salt-sensitive (Dahl SS) rats and their control salt-resistant (SS13BN) rats were randomly divided into six groups and fed for 8 weeks with normal salt (0.4% NaCl, NS), high salt (8% NaCl, HS), or high salt combined with clopidogrel gavage (10 mg/(Kg·d), HS+CLO). Arterial systolic blood pressure was continuously measured by the tail-cuff method over 8 weeks, and mean arterial pressure was measured by carotid cannulation after 8 weeks (56 days). Renal histopathology was observed by hematoxylin and eosin (HE) staining, renal inflammatory cell infiltration was detected by immunohistochemistry, peripheral blood platelet activation and platelet-leukocyte aggregation were analyzed by flow cytometry, and renal inflammation-related proteins TNF-α, IL-1β, IL-6, and key proteins in the p38MAPK/NF-κB signaling pathway were detected by immunoblotting. Results Compared with the NS group, Dahl SS rats HS group exhibited significantly increased blood pressure, aggravated renal tissue damage, increased inflammatory cell infiltration and expression of inflammatory cytokines, elevated peripheral blood platelet activation and platelet-leukocyte aggregation, and increased expression of p38MAPK/NF-κB signaling pathway proteins. Clopidogrel effectively alleviated these phenotypes induced by high salt in Dahl SS rats. Conclusions Clopidogrel alleviated high salt-induced salt-sensitive hypertension, and decreased? renal inflammatory responses and dysfunction in Dahl SS rats by inhibiting platelet activation and the p38MAPK/NF-κB signaling pathway.