BACKGROUND: Endometrial cancer, a malignancy linked with obesity, may be influenced by adipocytokines signalling due to chronic inflammation. This study explores the molecular expression patterns of adiponectin, leptin, interleukin6 (IL6), tumor necrosis factor (TNF)α, and their receptors in endometrial cancer patients and associations with lymphovascular space invasion (LVSI) and other tumour characteristics. METHODS: We analysed mRNA expression levels of the above biomarkers in endometrial cancer tissue using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), comparing them to benign endometrial tissue controls. Additionally, expressions in adipose tissue and lymph nodes were assessed, with correlations drawn between biomarker expression, patient demographics, and tumor characteristics. RESULTS: Using qRT-PCR analysis, endometrial cancer tissues (n = 39) exhibited higher expression levels of adiponectin, leptin, IL6, TNFα, and their receptors, IL6R and TNFRSF1A/B, compared to the calibrator sample, which consisted of five pooled benign endometrial control samples. Intriguingly, the adiponectin receptors, ADIPOR1 and ADIPOR2 demonstrated opposing correlations with cancer characteristics such as grade, histology, LVSI, and microcystic elongated and fragmented (MELF) pattern. LVSI was linked to increased levels of markers such as IL6R and ADIPOR2, along with decreased expressions of OBR (leptin receptor) and ADIPOR1, suggesting their potential as surrogate markers for diagnosing LVSI. Notably, higher adiponectin expression was observed in the cancerous lymph nodes of patients with LVSI, contrasting with those without LVSI. CONCLUSION: This study provides novel insight into differential role of adiponectin receptors in endometrial cancer and the associations of various markers with LVSI, emphasizing the need for tissue-specific biomarker assessments in determining treatment strategies.