Objective The aim of this study was to explore the protective effect of kaempferol against adriamycin-induced renal injury in rats and its underlying mechanism.Methods A rat model of renal injury was established by adriamycin injection. The rats were divided into the model group； the low-， medium-， and high-dose kaempferol groups； and the high-dose kaempferol + EX527 （silence information regulator 1 ［SIRT1］-specific inhibitor） group. A blank control group was also used （n = 10）. Twenty-four-hour urine protein levels were measured on the day of modeling and at 1， 2， and 4 weeks after modeling. Serum creatinine and blood urea nitrogen concentrations were measured using an automatic biochemical analyzer. The levels of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β） were measured by enzyme-linked immunosorbent assay. Hematoxylin and eosin staining was used to detect pathological changes in renal tissues. The ultrastructure of the kidneys was observed using transmission electron microscopy. Flow cytometry was used to observe renal cell apoptosis. Western blotting was used to detect the protein levels of SIRT1， p38-mitogen activated protein kinase （p38MAPK）， phosphorylated （p）-p38MAPK， nuclear factor-κB p65 （NF-κB p65）， p-NF-κB p65， B lymphocytoma-2 protein （Bcl-2）， Bcl-2-related X protein （Bax）， and caspase-3 in renal tissue.Results In the first week， the 24 h urine protein level increased in the model group compared to that in the blank control group. In the second and fourth weeks， the levels of serum creatinine， blood urea nitrogen， TNF-α， and IL-1β increased. The renal tissue injury score and the apoptotic rate also increased. The protein levels of p-p38MAPK/p38MAPK， p-NF-κB p65/NF-κB p65， Bax， and caspase-3 increased. SIRT1 and Bcl-2 protein expression levels significantly decreased （P < 0.05）. After intervention with low， medium， and high doses of kaempferol in the model rats， the aforementioned changes were significantly reversed （P < 0.05）. The SIRT1-specific inhibitor EX527 significantly downregulated the expression level of SIRT1 and significantly weakened the protective effect of kaempferol against kidney injury （P < 0.05）.Conclusion Kaempferol has a protective effect against adriamycin-induced renal injury， and the mechanism may be related to the upregulation of SIRT1 expression， the inhibition of p38MAPK signal pathway activation， and a reduction in renal cell apoptosis.