Healthy human pregnancy is associated with changes in food intake, body fatness, energy expenditure and insulin resistance. However, available knowledge is limited regarding the physiological basis of these changes. Published evidence suggests that so-called adipokines (i.e. leptin, adiponectin and resistin) have significant roles when such changes are established. We explored, throughout a complete pregnancy, relationships between total body fat (TBF), energy expenditure, insulin resistance (homeostasic model of insulin resistance, HOMA-IR) and serum concentrations of leptin, adiponectin and resistin. Such concentrations were assessed before pregnancy in gestational weeks 8, 14, 20, 32 and 35, and 2 weeks postpartum in twenty-three healthy women. TBF, BMR (n 23) and HOMA-IR (n 17) were assessed before pregnancy in gestational weeks 14 and 32 and 2 weeks postpartum. TBF (%) was correlated with HOMA-IR (r 0·68–0·79, P < 0·01) and with serum leptin (r 0·85–0·88, P < 0·001) before and during pregnancy. Serum leptin was correlated with HOMA-IR (r 0·53–0·70, P < 0·05) before and during pregnancy. Serum adiponectin was inversely correlated with HOMA-IR in gestational week 32 (r − 0·52, P < 0·05). When HOMA-IR was regressed on TBF (%), the slope of the regression line was 0·046 before pregnancy, which was significantly (P < 0·05) different from the corresponding value, 0·111, in gestational week 32. The results indicate that pregnancy has an enhancing effect on the relationship between body fatness and insulin resistance. This effect, possibly mediated by leptin, may represent a mechanism by which offspring size is regulated in response to the nutritional situation of the mother.