Introduction: The aim of the study was to investigate changes in the serum levels of adiponectin and TNF-alpha, as well as insulin sensitivity, and to elucidate the possible relationship among the parameters and negative energy balance during the periparturient period of dairy cows. Material and Methods: Thirty primiparous Holstein dairy cows were selected for the study. Blood samples were collected from each cow seven days before the expected calving date, on the calving day, and 7, 14, and 21 days after calving. Blood non-esterified fatty acids (NEFA), beta-hydroxybutyric acid (BHBA), glucose, insulin, adiponectin, and TNF- alpha levels were measured. Revised Quantitative Insulin Sensitivity Check Index (rQUICKI) was calculated using data on NEFA, insulin, and glucose concentrations. Results: When compared to prepartum levels, serum concentration of adiponectin significantly increased on day 21 postpartum. The rQUICKI increased and NEFA levels decreased on day 7 after parturition. Insulin and glucose levels decreased on days 7, 14, and 21 postpartum when compared with prepartum levels. BHBA levels decreased on day 21 and TNF- alpha concentration also decreased on days 7, 14, and 21 postpartum. Adiponectin levels positively correlated with NEFA during the preparturient period. Negative correlation was detected between adiponectin and rQUICKI on calving day and on 14th day after parturition. TNF- alpha concentration positively correlated with glucose levels on day 7 prepartum and on 21st day postpartum and with rQUICKI on 21st day postpartum. Negative correlation was detected between adiponectin level and insulin sensitivity. Conclusion: Based on the results of the study, we concluded that adiponectin could possibly increase insulin sensitivity when blood NEFA concentrations are elevated.