Background : Epidemiological studies showed a trend of increased incidence and prevalence rate of diabetes mellitus (DM). Endothelial dysfunction in DM lead to atherosclerosis, high level of osteoprotegerin can lead to endothelial dysfunction. Osteoprotegerin is mainly produced by bones, but is also secreted by cardiovascular structures, lungs, kidneys, hematopoietic and immune cells. Osteoprotegerin acts to prevent osteoclast activation and to neutralizes proapoptotic activity. Purpose : This study aimed to investigate relation of osteoprotegerin (OPG) serum level in diabetic mellitus (DM) rat model which had given physical exercise. Method : This study is an experimental research design with a post-test only control group to measure OPG level. Rat model of DM obtained by injecting streptozotocin 35mg/kgbw intra peritoneal Sprague Dawley male rats aged 11-12 weeks. Rats were divided into two groups, physical exercise (PE) and without physical exercise (WPE) group. Physical exercise using a special treadmill for rat, low to moderate intensity, frequency 5x/week for 9 weeks, with a week of adaptation using 5 m/min for 10 minutes, followed 8 weeks using a gradual rise of velocity, 5 m/min to 20 m/min for 60 minutes. Osteoprotegerin serum level was measured by enzyme linked immunosorbent assay (ELISA). Result : Mean of OPG in PE was lower than WPE. Result of Mann-Whitney test p value = 0,338, there is no significant statistically difference between the two groups. Conclusion : There is no statistically changes of OPG serum level of DM rat model with physical exercise. Physical exercise had not understand yet to influence OPG level. Key words: diabetes mellitus, exercise, osteoprotegerin