We investigated the acute and long-term effects of low-intensity resistance exercise (knee extension) with slow movement and tonic force generation on muscular size and strength. This type of exercise was expected to enhance the intramuscular hypoxic environment that might be a factor for muscular hypertrophy. Twenty-four healthy young males without experience of regular exercise training were assigned into three groups (n = 8 for each) and performed the following resistance exercise regimens: low-intensity [~50% of one repetition maximum (1RM)] with slow movement and tonic force generation (3 s for eccentric and concentric actions, 1-s pause, and no relaxing phase; LST); high-intensity (~80% 1RM) with normal speed (1 s for concentric and eccentric actions, 1 s for relaxing; HN); low-intensity with normal speed (same intensity as for LST and same speed as for HN; LN). In LST and HN, the mean repetition maximum was 8RM. In LN, both intensity and amount of work were matched with those for LST. Each exercise session consisting of three sets was performed three times a week for 12 weeks. In LST and HN, exercise training caused significant (P < 0.05) increases in cross-sectional area determined with MRI and isometric strength (MVC) of the knee extensors, whereas no significant changes were seen in LN. Electromyographic and near-infrared spectroscopic analyses showed that one bout of LST causes sustained muscular activity and the largest muscle deoxygenation among the three types of exercise. The results suggest that intramuscular oxygen environment is important for exercise-induced muscular hypertrophy.