The aim of this study was to investigate the effect of caffeine on the amplitude and rate of skeletal muscle contraction using frog sciatic nerve-gastrocnemius muscle model. Caffeine is a xanthine alkaloid whose use is widely unregulated. It is taken as a central nervous system stimulant in various foods and drinks. The effect of caffeine on skeletal muscle contraction and a possible elucidation of its mechanism of action were investigated. The sciatic nerve-gastrocnemius muscle preparation of the frog mounted on a kymograph was utilized. Varying doses of caffeine was added to the organ bath at 5, 10, 15, 20 and 25 mg/mL and its effect on skeletal muscle contraction was studied. The effects of caffeine preceded by administration of acetylcholine, atropine, nifedipine, magnesium chloride and calcium gluconate at 25 mg/mL were also studied. A dose dependent increase in skeletal muscle contraction (25.25±0.48, 49.00 ±1.23, 52.38±2.58, 59.25±1.11 and 68.50±0.87 mV; p<0.05) was observed on administration of increasing doses (5, 10, 15, 20 and 25 mg/mL, respectively) of caffeine respectively. While a significant reduction (0.90±0.04 mV) and increase (77.50±1.56 mV) in strength of contraction was observed on administration of nifedipine and calcium gluconate respectively. Administration of magnesium chloride caused a significant decrease in the strength of contraction (28.25±5.01) as compared to control. However, there was no significant difference in the contraction period and relaxation period between the treatment groups. The findings imply that caffeine increases skeletal muscle contraction and suggests it exerts the effect through increasing calcium ion release.