Objective: This study aims to assess the efficacy of clarithromycin (CAM) combined with fluticasone propionate (FP) in patients with chronic rhinosinusitis (CRS) after functional endoscopic sinus surgery (FESS), focusing on nasal function, nasal mucociliary transport (MCT) function, and serum inflammatory markers. Methods: The control group (n = 48) was treated with FESS alone, while the study group (n = 48) was treated with FESS plus CAM combined with FP. The clinical effects, symptom scores, nasal function, nasal MCT function, serum inflammatory marker levels, and the occurrence of adverse reactions were compared. Results: The total efficacy rate of the study group (95.83%) was significantly higher than that of the control group (83.33%). After treatment, the study group showed lower symptom scores for nasal congestion, runny nose, sneezing and dizziness, and headache compared to those in the control group. The study group also had lower nasal airway resistance, shorter distance from the minimal cross-sectional area to the nostril, and lower T&T olfactory scores. In contrast, their nasal cavity volume and minimal cross-sectional area were higher than those of the control group. Additionally, the nasal mucociliary clearance and MCT rates were higher in the study group. Serum levels of interleukin-6, interleukin-8, tumor necrosis factor-α, and procalcitonin were significantly lower in the study group compared to the control group (all P < .05). Conclusion: The use of CAM combined with FP in patients after FESS for CRS is effective, leading to the relief of clinical symptoms, improvement of nasal function, enhancement of MCT function, and reduction of inflammatory response, without increasing the incidence of adverse reactions.