The nonuniformity of infrared detectors directly affects the quality of infrared imaging and measurement accuracy. Ground-based infrared radiation measurement systems often can not occupy the full surface of the detector when imaging long-distance flying targets. In order to improve image quality, a method of nonuniformity regional correction based on calibration is proposed. Taking the cooled mid-wave infrared detector with a target surface of 640×512 as the experimental object, based on the two-point calibration method of blackbody calibration, the whole surface calibration algorithm and the algorithm proposed in this paper are used for verification. The results show that when the imaging area is less than 1/3 of the surface, the nonuniformity error after region nonuniformity correction is less than 0.002%. Compared with the full-target nonuniformity correction algorithm, this correction algorithm further reduces the nonuniformity by about 30% to 75%, and the reduction rate of the nonuniformity error is greater than 30%. After using the correction algorithm in this paper, the nonuniformity of each area is further reduced, and the visual effect of correction is further improved. Therefore, the correction method has certain engineering application value.