Abstract: OBJECTIVE To explore the pharmacist service mode combining diagnosis-related groups (DRGs) combined with clinical pathways and observe the change of clinical therapeutic effect and cost effectiveness for the designated patients with respiratory tract infections of the clinical pathways. METHODS The patients with respiratory infectious diseases who were treated in Yuxi People's Hospital from Feb. 2022 to Apr. 2024 were enrolled in the study, and the patients who were treated from Mar. 2022 to Feb. 2023 were assigned as the control group, and the patients who were treated from Mar. 2023 to Feb. 2024 were assigned as the intervention group, and the patients were divided into the DRGsES35 group, the ES33 group and the ES31 group according to the type of disease. The changes of costs and effects of clinical medical regimens were observed and compared among the three groups of patients after the full-process closed-loop intervention management of rational drug use including the review before drug administration (review before prescription), supervision during drug administration (clinical pharmacists' ward rounds, consultation, medication education, drug adjustment and medication monitoring) and assessment after drug administration (comments on prescription, comments on specialized drugs, analysis of rational drug use of clinical pathways). RESULTS The length of hospital stay and hospitalization costs were remarkably less in the 3 DRGs intervention groups than in the control group(P＜0.05); the rate of rational drug use was increased in the 3 DRGs intervention group, and the clinical effective rate of the ES31 group was increased(P＜0.05). As compared with the control group, the cost consumption index of the ES35 intervention group was decreased from 0.72 to 0.54, the ES35 group decreasing from 0.54 to 0.49, the ES31 group decreasing from 0.55 to 0.38. The time consumption index of the ES35 intervention group was decreased from 1.12 to 1.01, with the ES33 group decreasing from 0.85 to 0.84, the ES31 group deceasing from 0.73 to 0.63. As for the patients of the ES35 clinical pathway group, the analysis of economical efficiency of the different anti-infection drug therapies indicated that the cost-effectiveness ratio (CER) of the group C (the azithromycin group) was 3002.46, it was the absolute predominant regimen; the CERs of the group D (the cefuroxime group), the group A (the levofloxacin group) and the group B (the moxifloxacin group) were 3608.59, 3837.70 and 4237.43, respectively. CONCLUSIONS The novel pharmaceutical service mode of clinical pharmacists' interventions to rational drug use based on clinical pathways under the background of DRGs payment has remarkably reduce the hospitalization cost of the hospitalized patients with respiratory system infections and raise the rationality of drug administration and the clinical effective rate.