Objective To construct a diaphragm exercise program for patients with mechanical ventilation in intensive care unit(ICU),and to explore its clinical application effect. Methods Based on literature analysis and expert meeting,a diaphragm exercise program of ICU patients with mechanical ventilation was constructed. A total of 69 adult patients with mechanical ventilation in our comprehensive ICU from October 2020 to October 2021 were randomly divided into an experimental group(35 cases) and a control group(34 cases). The control group was given ICU routine rehabilitation nursing care and early activities,and the experimental group was given the diaphragm exercise on the basis of the interventions in the control group. End-inspiratory diaphragm thickness (DTei),end-expiratory diaphragm thickness(DTee),diaphragm thickening fraction(DTF) and diaphragmatic excursion(DE) were evaluated by ultrasound before and 24,48,72 and 120 hours after intervention. The success rate of weaning and the incidence of adverse events were compared and analyzed between the 2 groups. Results Repeated measures ANOVA showed that the time effect and interaction effect of DTei between the 2 groups were statistically significant(P<0.05);the time effect of DTee in the 2 groups was statistically significant(P<0.05);the time effect and interaction effect of DTF in the 2 groups were statistically significant(P<0.05);the time effect and interaction effect of DE in the 2 groups were statistically significant(P<0.05). The DTei of the experimental group was higher than that of the control group at 120 h after intervention;the DTF of the experimental group was higher than that of the control group at 72 h and 120 h after intervention;the DE of the experimental group was higher than that of the control group at 120 h after intervention;the differences were statistically significant(P<0.05). The weaning success rate of the experimental group was higher than that of the control group,and the difference was statistically significant(P<0.05). There were no adverse events such as sudden drop of oxygen saturation,tachycardia or musculoskeletal injury occurred in the 2 groups. Conclusion The diaphragm exercise program is safe and feasible for ICU patients with mechanical ventilation,which can improve diaphragm function,increase the success rate of weaning,and promote the rehabilitation of patients.