Background: Acne vulgaris is a self-limited" disease that mainly involves the sebaceous follicles. Systimic antibiutic is a common therapeutic modality, so bacterial resistance can be a problem. Objectives: Assesment of Propionibacterium resistance to erythromycin, tetracycline, clindamycin and spiramycin. Patients & Methods: Sampling was done on lesions of 123 patients with acne vulgaris who referred to dermatology clinic of Shahid Dr. Faghihi hospital in Shiraz. After isolation and confirmation of P. acnes, minimal inhibitory concentration (MIC) of above mentioned antibiotices were measured with agar dilution test. Results: From 123 patients, 129 samples were taken. Presence of P .acnes was confirmed in 62 samples. MICs for antibiotics were: tetracyclin 0.03 -0.125 /-1g/ml, erythromycin 0.015 -0.06 /-1g/ml, clindamycin 0.03-0.5/-!g/ml and spiramycin 0.015 - 0.25 /-1g/ml. Conclusion: The samples of P. acnes isolated from acne vulgaris lesions in this study were sensitive to above mentioned antibotics.