Objective To explore the effects of colostrum enemas on meconium evacuation and immune response in very low birth weight (VLBW) preterm newborns. Methods Totally, 128 VLBW preterm newborns were randomly assigned into 2 groups of 64 cases each. The intervention group received enema with 2mL/kg colostrum, while the control group received enema with 1 mL/kg glycerin suppository plus 1 mL/kg saline solution diluted at a ratio of 1∶1. Enemas started 24 hours after birth and ceased upon complete meconium evacuation. Results Ten cases in the intervention group dropped out, versus 9 cases in the control group. The intervention group had significantly shorter time to complete meconium evacuation, and time to full enteral feeding , as well as faster weight gain rate, than the control group (all P<0.05); the former group also had significantly higher immunoglobulin A (sIgA) concentration in the first and last meconium discharge sample, as well as in the first-time and sixth-day urine sample, than the latter group (all P<0.05). The intervention group also had significantly lower rates of necrotizing enterocolitis and feeding into-lerance than the control group (both P<0.05). Conclusion Colostrum enemas can facilitate meconium evacuation in VLBW preterm newborns, expedite full enteral feeding, enhance weight gain, boost immunity, and reduce incidence of related complications.