Objective To investigate the regulatory effects of thymosin α1 on autophagy adaptor protein SQSTM1/p62 and on sarcopenia in the aging mice. Methods Mouse myoblasts (C2C12) were divided into control group, dexamethasone group, dexamethasone+thymosin α1 group, and dexamethasone+thymosin α1+p62 silence group. In each group, the proliferative activity (OD at 450 nm wavelength) of cells was examined using cell counting kit-8, and the formation of C2C12 muscle tube cells was detected. In addition, 30 SAMP8 rapidly aging mice were divided into SAMP8 group, thymosin α1+SAMP8 group, and thymosin α1+p62 silence+SAMP8 group using random number table method, with 10 mice in each group. The ratio of lean body mass (LBM) to body mass (BM) [LBM/BM (%)] of each group was detected. The expressions of p62, myosin D (MyoD), myogon transcription factor (MyoG), myosin heavy chain (MyHC), muscle ring-finger protein 1 (MuRF1) and muscle atrophy related protein (MAFbx) in C2C12 and muscle tissues were detected by Western blotting. GraphPad PRISM 5.01 was used for statistical analysis. According to the data type, comparison between groups was preformed using t test. Results Compared with the control group, the proliferative activity and myotubule cell formation of dexamethasone group were significantly down-regulated (P<0.05 for both), the expression of p62, MyoD, MyoG and MyHC was decreased (P<0.05 for all), but the expression of MuRF1 and MAFbx was increased (P<0.05 for both). Compared with dexamethasone group, the proliferative activity and myoduct cell formation of dexamethasone+thymosin α1 group were significantly up-regulated (P<0.05 for both), and the expression of p62, MyoD, MyoG and MyHC was increased (P<0.05 for all), while the expression of MuRF1 and MAFbx was decreased (P<0.05 for both). Compared with dexamethasone+thymosin α1 group, the myoduct cell formation of dexamethasone+thymosin α1+p62 silence group was significantly decreased (P<0.05), and the expression of p62, MyoD, MyoG and MyHC was also decreased (P<0.05 for all). However, the expression of MuRF1 and MAFbx was increased (P<0.05 for both). Compared with SAMP8 group, the LBM/BM ratio of thymosin α1+SAMP8 group was significantly up-regulated (P<0.05), and the expression of p62 was increased (P<0.05), but the expression of MuRF1 and MAFbx was decreased (P<0.05 for both). Compared with thymosin α1+SAMP8 group, the LBM/BM ratio in+thymosin α1+p62 silence+SAMP8 group was significantly decreased (P<0.05), and the expression of p62 was decreased (P<0.05). But the expression of MuRF1 and MAFbx was increased (P<0.05 for both). Conclusion Thymosin α1 alleviates sarcopenia in the aging mice by activating SQSTM1/p62 signal.