Objective To investigate the role of Jiawei Sijunzi decoction (JSD) in delaying aging of mouse spleen tissue and its possible mechanism. Methods Forty 8-week-old male Kunming mice were evenly randomized into low-dose group, high-dose group, model group and control group (n=10). The aging models were established by intraperitoneal injection of 0.2 g/kg D-galactose in the low-dose, high-dose and model groups. The low-dose and high-dose groups were given JSD 1.6 and 6.4 g/kg by gavage, respectively, and the model group and control group were given the same volume of normal saline for 42 consecutive days. The pathological changes of the spleen tissue were observed, the spleen index was calculated, and the serum immunoglobulin G (IgG) level was detected. The mRNA expression levels of phosphatidylinositol 3-kinase (PI3K), p70 ribosomal protein S6 kinase (P70S6K) and eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1) of mammalian target of rapamycin (mTOR) signaling pathway were detected by quantitative real-time polymerase reaction (qRT-PCR). Results With obvious pathological changes, the spleen index and the serum IgG level of the model group were significantly lower than those of the control group (all P<0.05), while the mRNA expression levels of PI3K and P70S6K in spleen tissue were significantly higher than those in the control group (all P<0.05). The pathological changes of the spleen tissue in the high-dose and low-dose groups were lighter than those in the model group, the spleen index and the serum IgG level in the high-dose group were significantly higher than those in the model group (all P<0.05), while the mRNA expression levels of PI3K and P70S6K in the spleen tissue of the low-dose and high-dose groups were significantly lower than those of the model group (all P<0.05). Conclusion JSD can improve the aging degeneration of spleen tissue in mice, and the mechanism may be related to the inhibition of mTOR signal pathway.