The previously shown wave of β-cell apoptosis and the apparent plateau in the β-cell mass in the third week of life in rats are still unexplained events. Using a novel design-based stereological method we investigated the postnatal development of the β-cell population in Sprague-Dawley rats. The total β-cell mass increased from postnatal day 4 until day 16, to be followed by a plateau until day 24, after which it increased further. This plateau was caused by β-cell hypotrophia as well as decreased net β-cell formation. The β-cell mass per unit body weight (the relative β-cell mass) was five times higher at birth compared with the adult constant level that was reached at approximately 24 days of age. We propose an explanatory model for the postnatal development of the β-cell population in rats. According to this model, β-cells in the early postnatal period are immature, i.e. are not susceptible to the mechanism that in later life maintains a constant relative β-cell mass. Within the following weeks the number of mature β-cells increases, and from approximately day 24 and onwards the β-cell population is dominated by mature β-cells that adjust to match the body weight, keeping a constant relative β-cell mass. Findings of an apoptotic wave, a plateau phase in the total β-cell mass development, a period with β-cell hypotrophia, and the disappearance of insulin-like growth factor II positive β-cells at postnatal day 21 all fit well in the model.