Objectives: Estimation of serum resis-tin and TNF-α at time of pregnancy diagnosis and 6th gestational week (GW) to investigate its relation to de-velopment of gestational insulin re-sistance (GIR) and diabetes mellitus (GDM). Patients & Methods: All enrolled pregnant women underwent 75-Oral glucose tolerance test (OGTT) and ELISA estimation of serum resistin and TNF-α at baseline time and at the 6th GW. GIR was diagnosed using the homeostasis model assessment of IR (HOMA-IR) at score of >2 and GDM was diagnosed according to the results of the 75-OGTT if fasting blood glu-cose (FBG) was ≥92 mg/dl, 1-h post-prandial BG (PPBG) ≥180 mg/dl and 2-h BG ≥153 mg/dl. Study outcomes included the frequency of GIR and GDM, changes in serum levels of TNF-α and resistin throughout pregnancy and its relation to frequency and se-verity of GIR and GDM. Results: At the 30th GW, 112 women (34.9%) were IR and 39 women (12.1%) progressed to GDM. Serum resistin and TNF-α levels were signifi- cantly increased at 6th GW than base-line measures in all pregnant women with significant variance among study groups. Statistical analyses defined high baseline serum resistin as signifi-cant predictor for development of GIR and the hazard for being IR rises sharply with serum resistin above 5.5 ng/ml and high 6-GW serum TNF-α levels at cutoff points of serum TNF-α 10.79 ng/ml and 15.9 ng/ml as signifi-cant early predictors for development of GIR and GDM, respectively. Conclusion: Estimated serum resistin and TNF-α levels were positively asso-ciated with the risk for development of GIR and/or GDM later in pregnancy. Baseline serum resistin and 6-GW serum TNF-α levels could differentiate women susceptible to develop GIR and GDM, so could be used as early pre-dictors.