Muscle strain injuries disrupt the muscle-tendon unit, early rehabilitation is associated with a faster return to sports (RTS), but the time course of tissue healing remains sparsely described. The purpose was to examine tissue regeneration and the effectiveness of early versus delayed rehabilitation onset on functional and structural recovery after strain injuries. A total of 50 recreational athletes with a severe acute strain injury in their thigh or calf muscles were randomized to early or delayed rehabilitation onset. Magnetic resonance imaging (MRI) was obtained initially, 3 and 6 months postinjury, and dynamic contrast-enhanced MRI (DCE-MRI) estimated tissue inflammation initially and after 6 months. Muscle strength was determined 5 weeks, 3 months, and 6 months postinjury, and a questionnaire determined soreness, pain, and confidence. DCE-MRI microvascular perfusion was higher in the injured compared to an uninjured muscle acutely (P < 0.01) and after 6 months (P < 0.01), for both groups (P > 0.05) and unrelated to RTS (P > 0.05). Total volume of the injured muscle decreased from the acute to the 3-month scan, and to the 6-month scan (P < 0.01) in both groups. Muscle strength was similar in both groups at any time. There was a nonsignificant trend (P ≤ 0.1) toward less pain and higher confidence with early rehabilitation. One reinjury was recorded. In conclusion, our data showed prolonged tissue repair with the initial response linked to muscle atrophy but did not explain why early rehabilitation onset accelerated recovery considering that structural and functional recovery was similar with early and delayed rehabilitation.