The aim of this study was to investigate the effect of a one-rod levonorgestrel implant on the blood chemistry profile, including random blood glucose (RBG), haemoglobin (Hb), alanine transferase (ALT), aspartate transferase (AST), and the lipid profile, including total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides. This prospective cohort study was conducted at Raden Saleh Clinic, Jakarta, from 2010 to 2012. The implants were inserted subdermally in 30 patients. The subjects were evaluated every 6 month up to 2 years. Bivariate analysis using t-test or Wilcoxon signed rank test was performed for all variables. p < 0.05 was considered a significant value. The Hb, RBG, AST, and lipid profile levels were significantly different before and 6 months after one-rod implant insertion (p < 0.05). However, for 24 months, all of the parameters were still within normal limits and did not differ clinically. One-rod levonorgestrel implant insertion has a minimal effect on all blood chemistry profiles.