The aim of this study was to investigate the effect of two menstrual cycle phases and aerobic exhaustive exercise on plasma homocysteine and serum hs-CRP in female athletes. 9 female athletes with 8 years of regular club activity and regular menstrual cycle were selected for this study. They performed two Bruce protocols in their mid follicular and mid luteal phases up to exhaustion. Blood samples were gathered before and immediately after the exercise. One-way ANOVA test with repeated measures was used to investigate the changes of the two indicators in menstrual cycle phases (significant level 0.05). Basic and after exercise amounts of homocysteine and hs-CRP were higher during the follicular phase than luteal phase; this result was accompanied with an increase in estrogen in that phase. Only after the exercise amount of homocysteine during the follicular phase increased significantly. An increase in estrogen during the luteal phase reduced homocysteine and hs-CRP which suggested the protective role of estrogen against predictive factors of cardiovascular disease.