Granulocyte colony-stimulating factor (G-CSF), traditionally utilized in hematopoietic disorders, has garnered attention in reproductive medicine for its potential to enhance endometrial receptivity and improve pregnancy outcomes in assisted reproductive technology (ART). This study aimed to compare the effect of G-CSF administration via intrauterine infusion versus subcutaneous injection on pregnancy outcomes in infertile women undergoing IUI, 75 infertile women aged 18–40 years were enrolled and randomly assigned into three groups (n=25 each): Group 1 received 300 µg G-CSF via intrauterine infusion, Group 2 received 300 µg G-CSF via subcutaneous injection, and Group 3 served as the control with no G-CSF treatment. All participants underwent controlled ovarian stimulation followed by IUI. Endometrial thickness and sub-endometrial blood flow indices (PI, RI, V1/V2) were evaluated using Doppler ultrasound. Serum levels of TNF-α, IL-10, and VEGF were measured before and after G-CSF administration. Clinical pregnancy was confirmed by β-hCG testing two weeks after IUI and confirmation by transvaginal ultrasound. Both G-CSF intervention groups demonstrated significant improvements in sub-endometrial blood flow parameters compared to controls, with intrauterine infusion showing the most favorable Doppler indices (p<0.05). Additionally, intrauterine G-CSF administration resulted in upregulation of VEGF and IL-10 and a reduction in TNF-α levels, though differences did not reach statistical significance. Clinical pregnancy rates were higher in the intrauterine group compared to the subcutaneous and control groups, though differences did not reach statistical significance. Intrauterine infusion of G-CSF appears to offer superior benefits in enhancing endometrial receptivity, modulating inflammatory and angiogenic biomarkers, and improving pregnancy outcomes in IUI cycles compared to subcutaneous injection or no treatment. Further large-scale studies are warranted to validate these findings.