Photobiomodulation (PBM) therapy, formerly known as low-level laser therapy, has been widely used for tissue repair, pain relief, and anti-inflammatory and antimicrobial treatments [[1], [2], [3], [4]]. PBM exploits the absorption of visible and infrared light by chromophores in biological tissues to produce a series of reversible changes in structure and function of the target tissues that result in beneficial biological effects [5]. Importantly, the biological effects of PBM can be bidirectional, with the outcome (ineffective, beneficial, or harmful) depending on the wavelength and dose (power density and duration) of the irradiation [6]. Most studies have focused on the dose-dependent biphasic effects of PBM, which are commonly described using Arndt–Schulz law [[7], [8], [9], [10]]. This law suggests that there is a specific dose range within which the effects of PBM are beneficial. Below the lower threshold, PBM has no effect, and above the upper threshold, PBM produces inhibitory or harmful effects. Between these thresholds, the beneficial effect of PBM positively correlates with the light dose. The Arndt–Schulz law is accepted by most researchers, and many studies have verified such dose-dependent PBM biphasic reactions [6]. In addition, the wavelength of light is also thought to influence the biphasic effects of PBM, although no clear relationship between specific visible and infrared wavelengths and the stimulatory or inhibitory effects [3,11]. The outcome of PBM also depends on the identity of the target tissue [12]. The same light dose applied to different tissues, or different states of the same tissue, may produce opposite effects (i.e., stimulation or inhibition).

Inflammation is involved in important physiological and pathological processes in the human body. Moderate inflammation is the body's most powerful response to injury or invasion, but an excessive response leads to allergies or chronic inflammation [13,14]. PBM is considered to be an effective method of regulating inflammation. It also has a biphasic effects and is especially effective as an anti-inflammatory. PBM can stimulate the production of reactive oxygen species in normal cells while reducing their production in cells or tissues under oxidative stress. It can also activate nuclear factor kappa B (NF-κB) in normal cells but reduce the levels of pro-inflammatory factors in inflammatory cells [1,6,12,15]. However, there are few in vivo studies on the biphasic regulation of inflammation by PBM and no comparative studies on its pro- and anti-inflammatory effects in vivo. To understand the above effects on tissues in different inflammatory states in vivo, we used PBM to treat three wound models; namely, a common wound (normal level of inflammation), a wound infected with bacteria (high level of inflammation), and a diabetic wound (low level of inflammation).