The study is to design chitosan-coated pilocarpine nitrate submicro emulsion (CS-PN/SE) for the development of a novel mucoadhesive submicro emulsion, aiming to prolong the precorneal retention time and improve the ocular absorption.  CS-PN/SE was fabricated in two steps: firstly, pilocarpine nitrate submicro emulsion (PN/SE) was prepared by high-speed shear with medium chain triglycerides (MCT) as oil phase and Tween 80 as the main emulsifier, and then incubated with chitosan (CS) acetic solution.  The preparation process was optimized by central composite design-response surface methodology.  Besides the particle size, zeta potential, entrapment efficiency and micromorphology were investigated, CS-PN/SE’s precorneal residence properties and miotic effect were especially studied using New Zealand rabbits as the animal model.  When CS-PN/SE was administered topically to rabbit eyes, the ocular clearance and the mean resident time (MRT) of pilocarpine nitrate were found to be dramatically improved (P < 0.05) compared with PN/SE and pilocarpine nitrate solution (PNs), since the K_CS-PN/SE was declined to 0.006 4 ± 0.000 3 min⁻¹ while MRT was prolonged up to 155.4 min.  Pharmacodynamics results showed that the maximum miosis of CS-PN/SE was as high as 46.3%, while the miotic response lasted 480 min which is 255 min and 105 min longer than that of PNs and PN/SE, respectively.  A larger area under the miotic percentage vs time curve (AUC) of CS-PN/SE was exhibited which is 1.6 folds and 1.2 folds as much as that of PNs and PN/SE, respectively (P < 0.05).  Therefore, CS-PN/SE could enhance the duration of action and ocular bioavailability by improving the precorneal residence and ocular absorption significantly.