Introduction and Aim: Obesity is characterized by low-grade inflammation, which is depicted by an increase of proinflammatory cytokines and a decrease of anti-inflammatory cytokines. This study was designed to assess the changes of systemic adipokines and adipokines hepatic gene expression after laparoscopic sleeve gastrectomy (LSG). Patients and Methods: The current prospective work included 81 obese cases for whom LSG was done. Paired liver biopsies, weight changes, biomarkers for glucose homeostasis, and hepatic enzymes in addition to serum and hepatic mRNA gene expression of adipocytokines (adiponectin, leptin, resistin, and pre-B cell enhancing factor [PBEF]/Nampt/visfatin) were assayed at baseline and at 18 months after LSG. Results: At the end of follow-up period, the results showed that LSG significantly improved markers of glucose homeostasis, hepatic enzymes, in addition to both serum and hepatic expression levels of different adipokines. Moreover, our analysis showed a direct positive correlation between initial body mass index (BMI) and serum leptin, as well as a negative correlation between BMI and serum adiponectin values. Conclusion: Weight loss-induced LSG is parallelized with substantial amendments of insulin resistance in addition to changes of the serum and hepatic gene expression of adipokines toward antidiabetic and antiinflammatory profile.