The changes in the expression profile of the angiogenicgenes and serum biomarkers were investigated in the cows with the retained placenta after normal parturition. Retained fetal membranes (RFM) are considered one of the main reproductive disorders in dairy cattle. Highlight the effects of Excede® (Ceftiofur Crystalline Free Acid: Zoetis, USA) in combination with Oxytocin (Oxytocin®, each ml contains 10 IU oxytocin, ADWIA, Egypt), Estrumate® (250µg cloprostenol: synthetic analogue of PGF2ά) and Flunixin Meglumine® (nonsteroidal anti-inflammatory drug) on the reproductive performance in dairy cows. A total of 16 cows were allocated into two groups: group 1 (n = 8) the cows that have a normal loosed placenta, and group 2 (n = 8). The cows that have retained fetal membranes for more than 24 h after parturition. Blood with EDTA was collected from the tail vein for studying the expression of angiogenic proteins including vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor1 (VEGFR1), and RANTES genes. Serum was collected at a one-week interval before/after parturition for the study of biochemical changes. The VEGF expression decreased ten folds in cows with retained than normally dropped placentae (p ˂ 0.0001). The vascular endothelial growth factor receptor2 (VEGFR2) showed a threefold increase in cows with normal loosed than retained placentae (p˂0.01). The RANTES was increased in cows with retained rather than normal placentae by about 7 folds (p˂0.01). Phosphorus and total proteins were significantly lower (p˂0.05) in RFM cows one week after parturition. The serum albumin, TG, HDL, and cholesterol were significantly lower (p˂0.05) in RFM before, at, and after parturition. CPK was significantly higher in RFM before, at, and after parturition (p˂0.05). Increased values of MDA and decreased values of CAT, SOD, and R-GSH were detected in the blood of cows suffering from RFM (p˂0.05). Reproductive performance parameters for all studied cows were days to first estrous, number of service per conception and pregnancy rate. All reproductive parameters demonstrated significant (P < 0.05) changes between treated animals. The translation of VEGF and its receptor and RANTESmRNA at the time of parturition in dairy cows could be proxy biomarkers for the prediction of retained fetal membranes (RFM). In the same line, the activity of total proteins, serum albumin, TG, HDL, cholesterol, and CPK would be useful in the prediction of the RFM in dairy cows. Altogether, the obtained results indicated that retained fetal membranes in cows could be treated successfully without any interference by systemic injection of cephalosporin with caring of temperature. The reproductive performance criteria for all cows studied were the time of first estrus, the number of services per conception, and pregnancy rates. All parameters of reproductive performance showed significant changes (P < 0.05) among the treated animals. The results also indicated that cephalosporin can be used by systemic injection to treat placental retention with caring of the animal's temperature.