The interstitial fluid pressure (P_if) is important for maintaining constant interstitial fluid volume. In several acute inflammatory reactions a dramatic lowering of P_if has been observed, increasing the transcapillary filtration pressure and favoring the initial and rapid edema formation. This lowering of P_if seems to involve dynamic ₁-integrin mediated interactions between connective tissue cells and the extracellular matrix fibers (ECM). ₁-integrins are adhesion receptors responsible for the attachment of connective tissue cells to the ECM providing a force-transmitting physical link between the ECM and the cytoskeleton. Disruption of the actin filaments leads to lowering of P_if and edema formation, suggesting a role for the actin filaments. The aim of this study was to further investigate the role of the cytoskeleton in control of P_if by studying the effect of microtubuli fixation using paclitaxel and docetaxel. P_if was measured with the micropuncture technique. Albumin extravasation (E_alb) was measured using ¹²⁵I-labeled albumin. Paclitaxel and docetaxel were tested locally on foot skin in female Wistar rats. Paclitaxel (6 mg/ml) reduced P_if from -1.5±1.0 mmHg in controls to -4.9±2.6 mmHg after 30 min (p<0.05) in a dose-dependent manner (p<0.05). Docetaxel caused a similar lowering of P_if. Both paclitaxel and docetaxel increased E_alb compared to Cremophor-El® and saline control (p<0.05). Pretreatment with phalloidin prior to paclitaxel, causing fixation of the actin filaments abolished the lowering of P_if caused by paclitaxel. This study confirms several previous studies demonstrating that connective tissue cells influence P_if and edema formation.