Fibrotic processes in tissues are characterised by an excessive accumulation of collagen containing increased levels of pyridinoline cross-links, which has been taken as an important criterion to diagnose the fibrosis. Hypocrellin B (HB) is a natural photosensitizer with excellent photodynamic activity but very low dark-toxicity. In the current work, main purpose was to clarify if photodynamic action of HB could be applied to regulating the level of pyridinoline cross-link in collagen. To use gelatin as a model collagen, it was observed that the pyridinoline cross-link formation was effectively degraded by HB photodynamic action in the gelatin, suggesting the level of pyridinoline cross-link formation in collagen may be photodynamically regulated to a normal level. Furthermore, mechanism of the photodynamic action of HB was studied.hypocrellin B, photodynamic therapy, collagen, pyridinoline cross-link, fibrosis Photodynamic therapy (PDT), a non-invasive or minimally invasive therapy, has been a clinically routine treatment to tumors and some microvascular diseases [1][2][3][4] , while shortage of photodynamic drugs is a world-wide problem. Among the photosensitizers potentially usable for PDT, hypocrellins are well known for their excellent PDT activity and super low dark-toxicity [5][6][7] . Hypocrellins, including hypocrellin A (HA) and hypocrellin B (HB) (Figure 1), are the natural photosensitizers present in a fungus hypocrella bambusae growing mainly in Yunnan Province, China. For several decades, the photophysical, photochemical and photobiological properties were extensively studied, and some water-soluble particles were successfully prepared for drug-delivery purpose [8][9][10] . Recently, hypocrellins were proved to be promising for PDT reagent to treat some vascular diseases [3,4,11] . In principle, PDT action depends on photogenerated free radicals and reactive oxygen species (ROS), which is a molecular basis that PDT may be widely usable for various kinds of diseases.Fibrosis, which is the physiological repair incorrect result, has a common characteristic of over-amount accumulation of collagen (including I, III, IV and other types) in liver, kidney, lung, skin and so on. Recently, it was recognized that the level of pyridinoline cross-link was much higher than the normal [12][13][14][15][16] . In general, the formation of collagen cross-link in the biosynthesis of collagen fibrils is decided by two routes, namely the allysine route and the hydroxyallysine route [17][18][19][20] . In the fibrotic process, the collagen is cross-linked mainly via the hydroxyallysinecross-links such as the pyridinolines. In fact, the level of pyridinoline has been used as a symbol to diagnose fibrosis clinically [20][21][22][23] . It was also reported that the pyridinoline cross-link in the fibrotic skin could be photo-degraded by psoralen under the ultraviolet light [24] , and PDT could kill the P. aeruginosa in cys-