Background: The use of nanotechnology has led to rapid growth in various areas. Thus, health and safety issues of nanoparticles (NPs) should be promptly addressed. Manganese oxide (MnO2) nanoparticles (NPs) are typically used for biomedical and industrial applications. However, characterizing the potential human health effects of MnO2 NPs is required before fully exploiting these materials. The aim of this study was to investigate the toxicity of MnO2 micro- and nanoparticles on blood glucose level and lipid profile in male Wistar rats. Methods: A total of 105 rats were divided into one control and two experimental groups. Each experimental group received a single subcutaneous injection of MnO2 micro- and nanoparticles (100 μg/kg), respectively, every two weeks for 14 weeks. Their blood glucose, cholesterol, triglycerides, LDL, and HDL levels were then measured. The data presented as mean±SEM and compared with the repeated measures using the Prism statistical software (version 6.0).Results: Biochemical assessment in plasma samples showed that MnO2 micro- and nanoparticles injection significantly (P<0.01) increased the plasma glucose and cholesterol levels in all and few weeks, respectively. MnO2 nanoparticles significantly (P<0.01) decreased the HDL level in weeks 6, 12, and 14, but MnO2 microparticles decreased the HDL level only in week 12. In both MnO2 micro- and nanoparticles groups, LDL alterations were near to the control group, except for week 10. However, the same treatment had no effect on triglycerides concentrations compared to the control group.Conclusion: Our results show that exposure to nanosized particles at subchronic doses caused adverse changes in animal biochemical profiles, especially in glucose level. It seems that the high oxidative power of these particles is the main reason for these disturbances.