Antibacterial photodynamic therapy is a pioneering method for the inactivation of pathogenic bacteria. Four tetra alkyl-substituted cationic phthalocyanines with different hydrocarbon chains attached to the pyridyloxy group were synthesized. These photodynamic sensitizers were studied for antibacterial inactivation of a multidrug-resistant strain of Gram-negative bacterium Aeromonas hydrophila. Aeromonas species are recognized as etiological agents of a wide spectrum of diseases in humans and animals. The uptake of phthalocyanines by the bacterial cells decreased with an increase in cell density. Following the phthalocyanine solubility from hydrophilic to hydrophobic complexes, the accumulation capacity increased. Full inactivation was achieved with phthalocyanine with (methoxy) pyridyloxy substitution following a short exposure time, low drug concentration and mild irradiation. Although the phthalocyanine with the longest hydrocarbon chain (C12) has some toxic effect in the absence of light, substantial phototoxic effect was obtained with the optimal combination of drug-irradiation parameters.