Background: Acne vulgaris is a self-limited disease that mainly involves the sebaceous follicles. Systemic antibiotic is a common therapeutic modality, so bacterial resistance can be a problem. Objectives: Assessment of Propionibacterium resistance to erythromycin, tetracycline, clindamycin and spiramycin. Patients and 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.acne minimal inhibitory concentration (MIC) of above-mentioned antibiotics 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: Tetracycline 0.03-0.125 µg/ml, erythromycin 0.015-0.06 µg/ml, clindamycin 0.03-0.5 µg/ml and spiramycin 0.015-0.25 µg/ml. Conclusion: The samples of P.acnes isolated from acne vulgaris lesions in this study were sensitive to above mentioned antibiotics.