Objective To investigate the effect of progressive rehabilitation exercise in patients with mechanical ventilation in ICU. Methods A total of 80 patients receiving mechanical ventilation treatment in two wards of ICU of a tertiary Grade A hospital in Wuxi of Jiangsu Province from January 2021 to June 2022 were selected for this study. By unit convenience sampling method，they were divided into two groups，with 40 cases in each group. The control group received routine rehabilitation exercise nursing. The experimental group received early rehabilitation exercise through progressive rehabilitation exercise. Grip strength，sleep quality score，mechanical ventilation duration，length of stay in ICU，incidence of ICU acquired weakness （ICU-AW） and adverse events were compared between the two groups. Results Two patients in the experimental group and six patients in the control group withdrew midway，so 38 patients in the experimental group and 34 patients in the control group were retained. The grip strength and sleep quality score of the experimental group were higher than those of the control group， mechanical ventilation duration，ICU stay length and the incidence of ICU-AW of the experimental group were lower than those of the control group （P<0.05）. During the implementation of the study，there were no adverse events caused by rehabilitation training in the experimental group. Conclusion Progressive rehabilitation exercise can increase the grip strength of patients with mechanical ventilation in ICU，promote the recovery of body function， prevent the occurrence of ICU-AW，regulate the sleep quality of patients，and shorten the length of stay in ICU.