Lymphatic drainage from the peritoneal cavity occurs mainly via the subdiaphragmatic stomata and significantly reduces net ultrafiltration and solute clearances during long-dwell peritoneal dialysis. Intraperitoneal cholinergic drugs constrict these stomata and may reduce peritoneal cavity lymphatic absorption. We evaluated ultrafiltration kinetics, solute transport, and lymphatic drainage during single hypertonic exchanges in rats using 2.5% dextrose dialysis solution with and without added neostigmine. Net ultrafiltration was enhanced in the neostigmine group (p < 0.01) by a reduction in cumulative lymphatic absorption (p < 0.01) and without an increase in total transcapillary ultrafiltration during the dwell time. Likewise solute clearances were significantly augmented with neostigmine primarily due to the increase in dialysate drain volume (p < 0.01) since dialysate/serum solute ratios were unchanged. Pharmacological manipulation of peritoneal lymphatic absorption provides an alternative means of increasing the efficiency of long-dwell peritoneal dialysis without altering peritoneal transport of solutes and water.