1. The rumen adapts to increased food intake by the hyperplasia of epithelial cells. 2. Volatile fatty acids (VFA) stimulate cell mitosis of sheep ruminal epithelium in vivo. 3. Since VFA generally inhibit cell proliferation in vitro insulin was proposed in this study as the possible mediator of the mitotic stimulation in vivo. 4. Infusions (6 h) of insulin (0.125 U/kg per h) plus glucose (300 mg/kg per h) (n 5), and glucose alone (300 mg/kg per h) (n 2) resulted in higher mitotic index of biopsied rumen epithelium (MI) during 3 or 6 to 24 h after the start of infusion, and higher plasma immunoreactive insulin (IRI) and higher plasma glucose (PG) during the infusion. 5. Insulin plus glucose infusion showed higher MI, higher IRI, and lower PG than glucose infusion. 6. Sheep infused with saline for 6 h (n 1) showed no marked changes in MI, IRI, and PG. 7. Increased IRI by insulin plus glucose or glucose alone infusion was considered to stimulate cell proliferation in rumen epithelium. 8. Other possible mediations were discussed.