The optoacoustic method of monitoring absorbed optical energy distribution in tissues was employed to measure changes in glucose concentration in vivo. Glucose osmotic and hydrophilic properties cause reduction of tissue scattering as a result of glucose concentration increase around scattering particles and fibers. The opto-acoustic (OA) method utilizes time-resolved measurements of laser-induced ultrasonic profile in tissue resembling the distribution of absorbed optical energy. This opto-acoustic profile yields effective optical attenuation coefficient (μ eff ), which decreases with decrease of scattering. Glucose effect has been investigated initially in phantoms resembling optical properties of sclera (titanium dioxide (TiO 2 ) and polystyrene microspheres (PMS) water solution colored with potassium chromate, K 2 CrO 4 ) and then in sclera in vitro and in sclera of live rabbits. The forward mode of opto-acoustic detection was used in the experiments in vitro. Experiments were performed in ultra-violet (UV) spectral range at the wavelength of λ =355-nm. Experimental results demonstrated that an increase in glucose concentration from 5 mM to 60 mM was expressed in the 3% reduction of μ eff in aqueous solution of polystyrene microspheres. The effect of glucose on sclera in vitro was more prominent and measured as 10% reduction of μ eff with increase of glucose concentration from 1 mM to 50 mM. It was found that both the amplitude and the profile of OA signal were influenced by mechanical pressure applied to sclera specimen toward the surface of OA transducer. In experiments in live tissue, the backward detection mode was employed, as the only one side access to the tissue surface was available. In experiments in vivo the opto-acoustic profiles were measured in rabbit's sclera before and after intravenous glucose administering. The glucose concentration in rabbit blood was simultaneously measured using commercial device employing chemical analysis of blood. Experimental results demonstrated that a 1mM increase in glucose concentration resulted in a 3% decrease of optical attenuation in rabbit sclera in vivo. Such a pronounced change of optical scattering in sclera in response to physiologic change in blood glucose concentration encourages us to continue measurements in vivo and modeling glucose effect on tissue optics.