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Implants of progesterone resulted in an increased amount of insulin in plasma in response to intravenous administration of glucose in the rat. Isolated islets of Langerhans from progesterone-treated animals showed a greater maximum secretory response to glucose than islets from control animals but their sensitivity to low concentrations of glucose was unchanged. Theophylline increased glucose-induced secretion of insulin to a greater extent in progesterone-treated than in control rats and also produced a greater increase in the concentration of cyclic AMP in isolated islets from hormone-treated animals. These results suggest that the effect of progesterone on insulin secretion may be mediated by a change in cyclic AMP levels in the β cell. The possible role of progesterone in increasing the secretion of insulin in pregnancy is discussed.