Objective：To investigate the effect and possible mechanism of total flavonoids of Desmodium styracifolium（TFDS）on the formation of renal calcium oxalate stones. Methods：The selective macrophage Rictor gene knockout mice（Rictor^fl/flCre⁺ ）and their control group mice（Rictor^fl/flCre^- ）were used to establish renal calcium oxalate stone models，and the TFDS intervention was administered to the mice. We collected the kidney tissues from these two groups of mice for HE staining，immunohistochemical fluorescence staining，flow cytometry to explore the effect of TFDS on the formation of renal calcium oxalate stones. Primary bone marrow-derived macrophage（BMDM）from the two types of mice was extracted，and TFDS intervention was administered to investigate the mechanism through PCR，cell fluorescence staining，flow cytometry. Results：The number of renal calcium oxalate stones of the Rictor^fl/flCre⁺ mice was significantly higher than that in the Rictor^fl/flCre^- mice，accompanied by a significant increase in the polarization of M1 macrophages. After TFDS intervention in two groups of mice，the renal tissue of the TFDS + Rictor^fl/flCre^- group showed a significant decrease in renal calcium oxalate stones and M1 macrophage polarization，while the formation of renal calcium oxalate stones in the TFDS+Rictor^fl/flCre⁺ group showed no significant changes compared with the Rictor^fl/flCre^- group. Cell experiments showed that after the Rictor knockout，BMDM exhibited significant polarization of M1 macrophages，while the polarization of M1 macrophages was significantly reduced in the TFDS+BMDM group；however，there was no significant change in polarization after TFDS intervention in Rictor knockout of BMDM compared with that before intervention. Conclusion：TFDS may effectively and safely reduce the formation of renal calcium oxalate stones，possibly by inhibiting the Rictor regulated polarization of M1 macrophages.