(1) Purpose: This study aimed to examine whether a pneumatic cuff could promote muscle blood flow and improve muscle stiffness by continuously compressing muscles with air pressure in healthy college students. (2) Method: Twenty-one healthy collegiate students participated in this study. The probe of the near-infrared spectrometer was attached to the upper surface of the left gastrocnemius muscle, and a cuff was wrapped around the left lower leg. The cuff was inflated to 200 mmHg. After 10 min, the cuff was deflated, and the patient rested for 10 min. Muscle stiffness and fatigue were assessed before and after the intervention. (3) Results: During 10 min of continuous compression, StO2 continued to decrease until seven min of compression. After 10 min of continuous compression, StO2 was 30.8 ± 10.4%, which was approximately half of 69.2 ± 6.1% at rest. After the release of the pneumatic cuff compression, the StO2 remained higher than that at rest from 1 to 10 min. Muscle hardness was 19.0 ± 8.0 before intervention was 8.7 ± 4.8 after the intervention. Muscle fatigue was 6.6 ± 1.7 cm before the intervention and 4.0 ± 1.6 cm after the intervention. (4) Conclusions: This study suggests that sustained muscle compression using a pneumatic cuff can promote muscle blood flow and improve muscle stiffness and fatigue.