An experimental design was developed for morphometric analysis of the subcutaneous connective tissue after the subcutaneous injection of 0.1 ml of saline or a histamine solution (0.01, 0.1 or 1 0stamine dihydrochloride in saline). The subcutaneous connective tissue of 4-week-old rats, originally 170.0 ± 13.6 μm in thickness, swelled 5.2-fold at 15 min, 3.0-fold at 2 h, and 1.2-fold at 6 h after the injection of saline. The total cross sectional area of both blood and lymphatic vessels increased when compared to that at pre-injection (0.0186 ± 0.0030 mm2 in 6-mm-long specimen), 1.4-fold at 15 min, 2.2-fold at 2 h, and 1.1-fold at 6 h post-injection, while the total number of these vessels increased 1.1-fold at 2 h. The total cross sectional area of lymphatic vessels (0.0006 ± 0.0002 mm2 in 6-mm-long specimen) alone surged 7.7-fold at 15 min, 4.8-fold at 2 h, and 7.3-fold at 6 h. Collagen fibers were respectively highly, moderately, and mildly disorganized in arrangement at 15 min, 2 h, and 6 h after the saline injection. Histamine elicited an earlier, longer, and more pronounced vasodilatation, particularly at high concentrations. The transvascular permeability of Evans blue increased depending on the concentration of histamine. These findings indicate that the subcutaneous connective tissue has the ability to expand and store a considerable amount of fluid and reversibly returns to normal steady-state conditions by increasing fluid excretion into the blood and lymphatic vessels. It was also strongly suggested that the blood vessels are deeply involved in the excretion and volume regulation of the tissue fluid.