Breast cancer survivors may lose shoulder motion after life-saving treatments are completed. Exercises are applied countering these complications, but information about their biomechanical foundation is lacking. The PM muscle is often affected by cancer treatments, but strain occurring in the muscle during post surgical exercises is not known. The objectives of this study were to assess strain in the PM muscle during exercises prescribed following mastectomy. Methods: A 3-dimensional model of the shoulder and the PM muscle was used to interactively generate PM muscle strain during the simulated motions. Skeletal configurations were based on CT scans of two cadavers. Definitions of joint revolutes and muscle tendon paths were determined using literature reviews. Strains in the clavicular, mid-sternum and abdominal region of the PM muscle were calculated for applied shoulder exercises. Results: Averaged strain of the three regions ranged from 1% (flexion) to 21% (abduction) for single axis rotations and from 33% (abduction and external rotation) to 44% (overhead stretch) for combined motions. Regional strains ranged from -21% (shortening of the clavicular region during flexion) to 54% (mid-sternum region during the overhead stretch). Continuous data produced by the simulation allows the clinician to set strain limitations for each PM region for each motion. Discussion and Conclusions: From these simulation results it can be concluded that single motions fall within 30% strain, but combined motion may cause strain up to 54%. Differentials strains in the three regions occur during exercises, the least for shoulder abduction and extension. Future testing with patients needs to be performed to investigate the effectiveness and safety of the exercises designed using this simulation model.