Abstract: Background and Objective: Uterine fibroid is a gynecological disorder that causes infertility. Present study evaluated the protective effect of tinosporaside against the uterine fibroid (UF). Materials and Methods: Uterine fibroid was induced in all the animals by injecting diethylstilbestrol (2 mg mL–1, i.m.) for the period of 4 weeks. All the animals were separated in to five groups such as control, UF and Tinosporaside 1, 10 and 50 mg kg–1 receives tinosporaside (1, 10 and 50 mg kg–1, i.p.) 30 min before the injection of diethylstilbestrol for the duration of 4 weeks. At the end of protocol concentration of hormones (Estradiol and progesterone) in the serum was determined and later all the animals were sacrificed. Morphological features of uterus was estimated and activity of Nitric oxide synthase (NOS) and caspase 3 and the expressions of Bax, Bcl2, Akt and pAkt was estimated in the uterine tissues at the end of study. Results: Data of study revealed that treatment with tinosporaside significantly decreased the percentage of uterine coefficient and diameter of cervix compared to UF group. There was significant decrease in the serum concentration of estradiol and progesterone and activity of NOS in the uterine tissue of tinosporaside treated group compared to UF group. Moreover treatment with tinosporaside attenuated the altered expressions of several proteins (Bax, Bcl2, Akt and pAkt) in the uterine tissue of uterine fibroid rats. Conclusion: Present investigation concluded that tinosporaside protects the uterine fibroid by inducing the apoptosis of uterine cells.