The article presents and analyzes data from an experimental study conducted on white rats in females and males of reproductive age. The purpose of the study to study the morphometric and histological changes in the parenchyma of the lymph nodes of rats under the high-calorie diet (HCD) and with the correction of melatonin. The study was performed on 80 white rats of reproductive age. Microanatomy of the structural components of lymph nodes of white rats under physiological norms was examined in 10 intact animals. Experimental animals are divided into 5 groups. Statistical processing of digital data was performed using “Excel” software and “STATISTICA 6.0” using the parametric method. Eight weeks after HCD, there was a significant decrease in the relative area of the cortical substance in the parenchyma of lymph nodes of white rats of males and females by 10.3 % and 8.3 %, respectively, and an increase in the relative area of the medullary substance by 16.1 % and 13.2 %, respectively, greater than the intact animal group parameter. Corticomedullary index (CMI) decreased by 22.9 % and 19.0 %. After six weeks of HCD and the next six weeks of standard vivarium diet and melatonin administration, the relative area of cortical substance in the parenchyma of lymph nodes of white rats in males and females was 2.0 % and 2.9 %, respectively, greater than the parameters of the intact group of animals. Accordingly, the relative area of the medullary substance is 3.1 % and 4.6 % less than the parameters of the intact group of animals. CMI in both male and male rats was 5.1 % and 7.6 %, respectively, greater than the intact animal group parameter. Under the conditions of melatonin correction, it was found that on the histological preparations of lymph nodes the vein and artery were full-blooded. Empty hemocapillaries with thickened wall are observed. In the paracortical region, the number of high endothelial capillary venules decreases. Thus, long-term administration of melatonin improves the morphometric parameters of the parenchyma of the lymph nodes of rats, restores the morphological structure of the organ.