Objectives: To examine the differences in serum leptin levels and other relevant factors between male methamphetamine (METH) abusers during early abstinence and healthy controls. Methods: Fifty-five male METH abusers less than 2 weeks after quitting and 50 male healthy controls were enrolled. Abstinence was confirmed by daily negative urine drug screening results. Baseline body data included age, BMI, current smoking, smoking amount, abdominal subcutaneous fat thickness (ASFT), current daily exercise consumption (CDEC), hemoglobin, fasting glucose, total cholesterol, triglyceride, thyrotropin concentrations and other neuroendocrine axis hormones levels. Among these hormones, total testosterone (TT), estradiol, prolactin, cortisol and adrenocorticotropic hormone (ACTH) were measured through chemiluminescent immunoassays, and epinephrine and norepinephrine were detected using radio immunoassay, and leptin was measured using enzyme-linked immunosorbent assays. Results: Compared with the healthy controls, the male METH abusers during early abstinence had lower ASFT, CDEC, leptin, and TT levels and increased daily smoking, estradiol, cortisol, ACTH, and prolactin levels. A nonparametric Spearman's correlation analysis showed that CDEC was positively correlated with serum leptin, but cortisol, ACTH, and norepinephrine were negatively correlated with leptin in male METH abusers. A multivariate stepwise regression analysis indicated that Ln-cortisol and CDEC were independently associated with Ln-leptin in male METH abusers during early abstinence and in the controls. Conclusions: Male METH abusers during early abstinence had low serum leptin, which was associated with their body activity states and specific hormones from the HPA axes. Decreased cortisol levels and HPA axis dysfunction might lead to reduced activity and decreased leptin levels.