Background: Mycobacterium seedling is rich in co-antigens and, a good immunomodulator with bidirectional immunomodulatory function. Objectives: The present study aimed to explore whether the Mycobacterium vaccae vaccine can improve the incomplete immune recovery of acquired immunodeficiency syndrome (AIDS) patients. Methods: According to the number of patients receiving human immunodeficiency virus (HIV) long-term treatment in the Ninth People’s Hospital of Chongqing, China, 100 patients with HIV-RNA quantitation of less than 103 cepies/ml, CD4 + T cell count less than 500/UL, and CD4+T cell count of more than 50/UL after 3 years of Haart treatment were selected. In total, they were randomly assigned to one of three groups, one group received an intramuscular injection of M. vaccae vaccine, one group received an intramuscular injection of growth hormone, and the last group received only a placebo injection. The levels and changes of naive T cells, Treg cells, total CD4+ T cells, T helper 1 (Th1), T helper 2 (Th2) cells, and interleukin 7 (IL-7) cytokine were measured at baseline and after 12, 48, and 50 weeks. Results: After 48 weeks of treatment, the total CD4+T cells, Th1 cells, and naive T cells in AIDS patients increased, while IL-7 cytokines, Treg cells, and Th2 cells decreased in M. vaccae vaccine and growth hormone group. There was no change in the placebo group, indicating that M. vaccae vaccine and growth hormone can improve the immune function of AIDS patients. After treatment, in group A (M. vaccae vaccine), there was an increase in the total CD4+T cells, Th1 cells, and naive T cells as well as a decrease in Treg cells, Th2 cells, and IL-7 cytokines. The only significant difference between M. vaccae vaccine and growth hormone groups was a decrease in Th1 cells in the M. vaccae vaccine group. After a 12-week follow-up, it was found that there were no cases of secondary infection in the M. vaccae vaccine group, one case in the growth hormone group, and five cases in the placebo group, demonstrating that the secondary infection rate in M. vaccae vaccine and the growth hormone groups was lower than that in the control group. Conclusion: The M. vaccae vaccine may decrease the levels of IL-7 as well as Treg and Th2 cells by increasing the levels of CD4+T cells, Th1 cells, and pure T cells in AIDS patients, leading to the improvement of immune reconstitution of AIDS patients to some extent.