Objective:To assess the therapeutic efficacy and histopathological effect of photodynamic therapy (PDT) with intralesional injection of aminolevulinic acid (ALA) in a rat model of acneiform inflammatory nodules.Methods:Forty specific pathogen-free (SPF) SD rats were randomly and equally divided into normal control group, model control group, ALA injection group and topical ALA group. Rats in the normal control group received no treatment, and those in the other 3 groups were inoculated with Propionibacterium acne suspension on the right auricle for the establishment of a rat model of acneiform inflammatory nodules. After successful modeling, rats in the model control group received no other treatment, those in the ALA injection group were intranodularly injected with 5% ALA followed by red light irradiation, and those in the topical ALA group were topically treated with 5% ALA on the acneiform inflammatory nodules followed by red light irradiation. The treatment was performed once a week for 2 weeks. Twenty-four hours after the last treatment, general appearance and histopathological changes of rat ears were observed in each group, the thickness of rat auricles was measured, and liver and kidney functions were evaluated. Statistical analysis was carried out by using one-way analysis of variance and least significant difference- t test for comparisons among the groups. Results:The thickness of rat auricles significantly differed among the normal control group, model control group, topical ALA group and ALA injection group (0.435 ± 0.006, 1.269 ± 0.071, 1.088 ± 0.098, 0.699 ± 0.095 mm, respectively, F = 235.60, P < 0.001) , and was significantly higher in the model control group than in the normal control group, topical ALA group and ALA injection group ( t = 24.18, 5.24, 16.48 respectively, all P < 0.01) , but significantly lower in the ALA injection group than in the topical ALA group ( t = 11.24, P < 0.01) . Compared with the model control group, the topical ALA group and ALA injection group showed decreased degree of local redness and swelling as well as number of nodules on the rat auricle, and decreased quantity of infiltrating inflammatory cells in the dermis and subcutaneous tissues. Compared with the topical ALA group, nodules regressed more markedly in the ALA injection group, and no clumps of inflammatory cells or microabscesses were observed in the ALA injection group. There was no significant difference in levels of alanine aminotransferase, aspartate aminotransferase, creatinine or urea nitrogen among the 4 groups (all P > 0.05) . Conclusion:PDT with intralesional injection of ALA is more effective for the treatment of acneiform inflammatory nodules in rat models than PDT with topical application of ALA.